Combined effects of slow movement training with tonic force generation and aerobic exercise prior to cancer therapy in patients with lung cancer (START-lung): A pilot feasibility trial

Combined effects of slow movement training with tonic force generation and aerobic exercise prior to cancer therapy in patients with lung cancer (START-lung): A pilot feasibility trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Combined effects of slow movement training with tonic force generation and aerobic exercise prior to cancer therapy in patients with lung cancer (START-lung): A pilot feasibility trial Utae Katsushima, Takuya Fukushima, Jiro Nakano, Kazuki Fujii, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6341600/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Sep, 2025 Read the published version in BMC Cancer → Version 1 posted 9 You are reading this latest preprint version Abstract Background Exercise is known to improve physical function, quality of life, and treatment outcomes in patients with cancer. However, the feasibility and impact of implementing an exercise program from the first visit for suspected advanced lung cancer to treatment initiation remain unclear. This study aimed to evaluate the feasibility of a structured exercise program during this period. Methods This prospective, single-center study included patients with suspected advanced lung cancer who were instructed to perform a pre-treatment 4-week exercise program consisting of slow movement training with tonic force generation and aerobic exercise. Attendance rates and adverse events were assessed, and changes in physical function, muscle strength, and quality of life were evaluated. Patient feedback on the exercise program was collected. Results A total of 17 patients were analyzed, with a mean age of 70 years. The overall exercise attendance rate was 159.7 ± 54.4%. A high attendance rate (≥ 70.8%) was achieved by 15 patients without any adverse events. Significant improvements from baseline to after-exercise intervention were observed in the five-time sit-to-stand test and 30-second chair stand test. No significant changes in physical function, muscle strength, or quality of life were observed. Patient feedback indicated that exercise was beneficial in alleviating anxiety and maintaining physical condition during the waiting period before treatment. Conclusions A structured exercise program initiated from the first visit to treatment initiation was feasible and safe in patients with advanced lung cancer. Further studies, including randomized controlled trials, are warranted to assess its impact on clinical outcomes and long-term patient wellbeing. Trial registration UMIN000055155. Date of registration: August 5, 2024. advanced lung cancer aerobic exercise muscle strength physical function feasibility slow training Figures Figure 1 Background Lung cancer generally has a poor prognosis, with high mortality and morbidity rates [ 1 , 2 ]. However, in recent years, prognosis has improved with the emergence of immune checkpoint inhibitors and molecular targeted therapies [ 3 – 5 ]. Specialized tests, such as the assessment of programmed cell death ligand 1 (PD-L1) expression and genetic mutation analysis, are required for a definitive diagnosis of lung cancer and to determine an appropriate treatment plan [ 3 – 6 ]. Previously, we reported that the median time from the first visit to the initiation of treatment was 37 days for early-stage lung cancer and 42.5 days for advanced lung cancer [ 7 ]. During this period, body and muscle weight, physical function, and nutritional status declined, which may contribute to the development of cachexia, particularly in patients with advanced lung cancer [ 7 ]. Furthermore, physical function declines rapidly following a cancer diagnosis, and this decline tends to persist [ 8 ]. Notably, muscle weakness and reduced physical function have been associated with poor cancer prognosis [ 9 – 12 ]. However, no studies have examined the safety and adherence rates of exercise interventions during this period in patients with advanced lung cancer. Therefore, this study aimed to develop a structured exercise program for patients suspected of having advanced lung cancer to be implemented from the first visit to treatment initiation. We hypothesized that our exercise program could be safe, feasible, and prevent muscle weakness and physical function. Methods Study design and patients This was a single-arm feasibility study involving a single-center prospective intervention conducted at Kansai Medical University. Inclusion criteria Men and women aged ≥ 20 years (at the time of consent) with suspected advanced lung cancer and a scheduled first visit to the outpatient clinic for thorough examination and treatment were included in the study. All patients provided informed consent after receiving a detailed explanation of the study. Exclusion criteria Patients who had severe hepatic or renal dysfunction, were pregnant or lactating, had respiratory failure requiring oxygen therapy or severe pain interfering with physical function assessment, or were deemed unsuitable for participation by the principal investigator were excluded from the study. Exercise protocol Exercise protocol Patients were advised to engage in home-based exercise for at least a total of 6 sessions per week, including a minimum of three resistance exercise sessions (slow squats) and three aerobic sessions (walking for at least 30 min per session) for 4 weeks. The first visit (T0) was defined as the day of the first visit ± 7 days, and the intervention period (T1) was 4 ± 2 weeks from T0. Attendance was monitored through an exercise diary, with assessments conducted at both T0 and T1. The exercise diary was collected at T1 to gather patient feedback on adherence to the home-based exercise program. As recommended by the American College of Sports Medicine (ACSM) guidelines, the exercise program included both resistance and aerobic exercises, performed for at least 150 min per week [ 13 ]. For resistance exercise, participants performed slow squats, a movement involving controlled force generation [ 14 ]. They were instructed to squat until their thighs were parallel to the floor over 4 s, then extend their knees over another 4 s. Patients were advised to complete three sets of 10–15 repetitions for one session. If balance was a concern, they were permitted to hold onto a chair or wall for support. For aerobic exercise, patients were instructed to walk at moderate intensity (Borg scale: 12–14). Each walking session lasted at least 30 min. At the first visit, a physician counseled patients on the role of exercise in cancer treatment, while a physiotherapist provided detailed instructions for the home-based exercise regimen. Endpoints Primary endpoint The primary endpoint was the attendance rates of exercise sessions. Based on the report by Adamsen et al. [ 15 ], an attendance rate of 70.8% (17/24 sessions) or higher was considered feasible. This evaluation was based on exercise diaries, with attendance defined as the percentage of participant sessions out of six weekly sessions (24 total) over the 4-week period. Secondary endpoints The secondary endpoints included adverse events, physical activity (assessed using the Global Physical Activity Questionnaire [GPAQ]), health-related quality of life (QoL) (assessed using the EQ-5D), skeletal muscle mass, 6-min walk distance, grip strength, knee extensor strength, five-time chair stand test, 30-s stand test, one-leg stand time, and nutritional status (using the Mini Nutritional Assessment Short-Form [MNA-SF]). Additionally, lung cancer characteristics, baseline patient information, and blood laboratory data were collected from medical records. Physical activity The GPAQ was developed by the World Health Organization to assess physical activity and consists of 16 questions [ 16 ]. It collects information on physical activity levels and sedentary behavior across three domains: work, mobility, and leisure-time activity. The GPAQ is a reliable tool for assessing physical activity levels in cancer survivors [ 17 , 18 ]. In this study, patients were asked to complete the GPAQ at T0 and T1. Health-related QoL The EQ-5D is a standardized questionnaire for assessing health-related QoL (HRQoL). It consists of five components: mobility, personal care, daily activities, pain/discomfort, and anxiety/depression. Each component is rated on a 3- or 5-point scale to assess overall health status. In previous studies, the EQ-5D demonstrated adequate reliability and validity in assessing QoL in patients with cancer [ 19 ]. In this study, the EQ-5D was administered to patients at T0 and T1. Skeletal Muscle Mass A body composition analyzer (MC-780A-N, Tanita, Tokyo, Japan), utilizing the bioelectrical impedance analysis method, was used to evaluate body composition. From the data, we calculated the skeletal muscle mass index (SMI; kg/m 2 ) 6-Min Walk Distance The 6-min walk distance test is a simple and practical method for assessing functional exercise tolerance in patients [ 20 , 21 ]. In a straight, flat corridor, patients were instructed to walk for 6 min at the fastest, comfortable pace possible, continuing as long as they could. Resting was permitted if necessary. At the end of 6 min, the total walking distance (in meters) was recorded. Grip strength Muscle weakness was defined as grip strength < 28 kg in men and < 18 kg in women, based on the diagnostic criteria for sarcopenia [ 22 ]. Grip strength was measured using a hand-held dynamometer (HHD) (GRIP-D; Takei Scientific Instruments Co., LTD, Niigata, Japan). One test was performed for each hand, and the result of the stronger hand was used for analysis. Knee Extensor Strength Knee extension strength serves as an indicator of quadriceps (front thigh) muscle strength, while knee flexion strength reflects biceps femoris (back thigh) muscle strength. In this study, an HHD was placed on each leg for two measurements, with the higher value recorded as the final strength measurement. For the assessment, patients were seated in a final sitting position, with the trunk held upright and arms crossed over the chest. Afterwards, the examiner positioned the HHD on the front surface of the patient’s distal lower leg, securing it with a fixation strap. The patient was then instructed to extend the knee with maximum force to measure isometric knee extension muscle strength [ 23 ]. Five-time chair stand test Patients were instructed to sit in a chair with their arms crossed over their chest and their back against the chair. The time required to rise from a seated position to a full standing position and return to sitting five times was recorded. Muscle weakness was defined as a test duration of ≥ 11.19 s[ 24 ]. 30-s chair stand test The 30-s chair stand test assesses lower limb muscle activity, balance ability, and walking speed. It is conducted by counting the number of times a participant can rise from a seated position in a chair within 30 s [ 25 ]. For this test, participants were seated in a chair without armrests, with arms crossed over the chest, and were instructed to stand up and sit down repeatedly for 30 s. The total number of completed repetitions was recorded. One-leg standing test With both hands on the hips and eyes open, participants raised one leg 5 cm off the ground, and the duration of their balance was measured. After one or two practice trials, each leg was measured twice, with the longest recorded time used for analysis. Motor instability was defined as an inability to balance for more than 15 s on one leg [ 26 ]. Nutritional status Nutritional status was assessed using the MNA-SF, an internationally standardized tool with established reliability and validity. The MNA-SF is a simple, efficient screening tool that requires no specialized knowledge or equipment and can be completed within minutes [ 27 ]. It was administered to each patient on their first visit to the rehabilitation outpatient clinic. Statistical methods The expected rate of exercise implementation, the primary endpoint of this study, was set at 70.8% (attended 17/24 sessions) based on a study by Adamsen et al [ 15 ]. The threshold was set at 42 ± 34%, based on findings from Mazzoni et al [ 28 ]. Statistical parameters were set as follows: alpha error = 0.05, beta error = 0.05. The required sample size was calculated as 17 participants. To account for a 20% dropout rate, the final target sample size was set at 21 participants. Each exercise session was counted as one implementation, regardless of the number of sets, resistance exercises, or the duration of aerobic exercise. For secondary endpoints, data collected at T0 and T1 were presented as means ± standard deviation. Paired t -tests were used to compare measurements at T0 and T1, with mean differences and 95% confidence interval (CI) calculated. The significance level was set at p < 0.05. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, NY, USA). Ethical considerations This study was approved by the Research Ethics Review Committee of Kansai Medical University Hospital, Osaka, Japan (approval number: 2024037), and was registered in the University hospital Medical Information Network (UMIN000055155). Written informed consent was obtained from each participant. All procedures were performed in accordance with the ethical standards of the committees responsible for human experimentation (institutional and national) and the Declaration of Helsinki of 1964 and its later versions. Results Patient enrollment and baseline characteristics A total of 24 patients were recruited between August 1 and October 28, 2024. As illustrated in the flowchart (Figure 1), one patient declined participation due to general fatigue, another was uninterested in exercise, and a third withdrew due to fatigue and pain. Ultimately, 21 patients were enrolled. However, two patients developed obstructive pneumonia between the first visit and the start of treatment; one patient died due to disease progression, and another was excluded from the analysis after a benign tumor was diagnosed following further examination. Consequently, the final cohort for analysis included 17 patients. The baseline characteristics of these 17 patients are presented in Table 1. The mean age was 70 years, with 14 men (82.4%) and three women (17.6%). At the first visit, five patients (29.4%) had a performance status (PS) of 0, while 12 patients (70.6%) had a PS of 1. The stage of disease at confirmed diagnosis varied, with two cases (11.8%) classified as stage I, three cases (17.6%) as stage IIIA, two cases (11.8%) as stage IIIB, one case (5.9%) as stage IIIC, five cases (29.4%) as stage IVA, and four cases (23.5%) as stage IVB. Overall exercise attendance rate The overall exercise attendance rate was 159.7 ± 54.4%. Among the 17 patients, 15 patients maintained a high attendance rate (attended at least 70.8%), while two patients demonstrated low attendance. Patient feedback regarding exercise participation at T1 is summarized in Table 2. Among the 15 patients with a high exercise attendance rate, several had pre-existing exercise habits, while others credited family support as a motivating factor. Some found that exercising provided emotional stability, whereas others believed it would impact their cancer treatment by contributing to build muscle strength and dispelling anxiety. In the two cases with a low exercise attendance rate, physical symptoms, prior exercise preferences, and environmental factors contributed to non-adherence. Safety Among the 17 patients, there were no apparent adverse events associated with the exercise program. Changes in physical activity, QoL, Skeletal Muscle Mass, physical function, and nutritional status from the first visit to the start of treatment As summarized in Table 3, the patients demonstrated significant improvements in both the five-times-sit-to-stand test (mean difference: -1.4 s, 95% CI: -2.1 to -0.8 s, p <0.001) and 30-s chair stand tests (mean difference: 3 times, 95% CI: 2 to 4 times, p <0.001) after exercise intervention. However, no significant changes were observed in muscle strength (grip strength mean difference: 0.8 kg, 95% CI: -0.2 to 1.9 kg, p =0.093; isometric knee extensor strength mean difference: 1.5 kgf; 95% CI: -0.1 to 3.1 kgf; p =0.064), physical function (6MWD mean difference: 11 m, 95% CI 12 to 34 m, p =0.336; OLS mean difference: 0.5 s, 95% CI: -0.5 to 1.5 s, p =0.276), muscle mass (SMI mean difference: 0.1 kg/m 2 , 95% CI: 0.04 to 0.16 kg/m 2 , p =0.240), nutritional status (MNA-SF mean difference: 1 point, 95% CI: 0 to 2 points, p =0.135), physical activity (GPAQ mean difference: 48.2 min/week, 95％ CI: -2186.7 to 2090.3 min/week, p ＝0.962), or QoL (EQ5d-5L mean difference: 0.05 points, 95% CI: -0.02 to 1.11, p =0.143). Discussion This study is the first prospective trial to evaluate the feasibility of exercise during the period between a patient’s initial visit to an outpatient clinic and the start of lung cancer treatment. This investigation is particularly novel, as no previous clinical trials have examined exercise interventions from the time of the first visit for suspected lung cancer to the start of treatment, a period even earlier than conventional pre-treatment exercise interventions. The results of this study support our hypothesis, demonstrating that our exercise program was exceptionally feasible and safe. Exercise in cancer survivors has been shown to reduce mortality and recurrence risk, alleviate cancer-related fatigue, improve QoL, reduce depression and anxiety, enhance sleep quality, and improve cardiorespiratory function [ 29 – 33 ]. The American Cancer Society and the American College of Sports Medicine recommend a combination of 150 min of moderate-intensity aerobic exercise per week and at least two sessions of resistance training [ 29 , 34 ]. However, in the absence of studies defining a feasible and optimal exercise regimen for patients with cancer during the period between their initial outpatient visit for suspected advanced lung cancer and definitive diagnosis, we based our guidance on the above recommendations. Our results demonstrated a high attendance rate of 159.7 ± 54.4%. Previous studies have reported that exercise programs for patients with advanced lung cancer often face challenges such as high dropout rates and low adherence [ 34 , 35 ]. Furthermore, while supervised exercise interventions have been shown to be feasible for patients with advanced cancer [ 36 , 37 ], the feasibility of implementing home-based exercise programs has remained unclear. This study confirmed the high feasibility of aerobic exercise and slow squats, which are simple and easily integrated into daily routines [ 38 ]. Furthermore, patient feedback indicated that these exercises could be performed year-round, regardless of weather conditions or living environment, and without requiring specialized equipment or designated space. These factors likely contributed to the high attendance rate observed in our study. However, various physical symptoms, such as pain and shortness of breath, along with individual exercise preferences, lifestyle factors, and living environment, may act as barriers to adherence. In addition, the waiting period between a patient’s first visit—when they receive the distressing news that they may have cancer—and the start of treatment following diagnostic tests is often marked by heightened anxiety regarding their prognosis and treatment course. In the present study, educating patients about the significance of exercise in cancer treatment at the time of the first visit may have facilitated behavioral changes, leading to a high exercise attendance rate. In addition, the benefits of exercise on fatigue, QoL, and depression in patients with cancer have been previously reported [ 39 ]. Patient feedback suggests that engaging in exercise from the initial visit to the start of treatment not only improves physical function but may also help alleviate mental distress, including anxiety and depression. A previous study reported significant weight loss, deterioration in nutritional status, and reduced grip strength between the first visit and the start of treatment [ 7 ]. However, notably, the results of this study demonstrated that exercise therapy during this period prevented an obvious decline in physical function, nutritional status, or QoL. Moreover, improvements were observed in the five-time sit-to-stand and 30-s chair stand ( p < 0.001), both indicators of lower limb muscle strength. It showed that the slow squat causes increases in muscle mass and strength by sustaining tonic muscle contractions and generating continuous force production [ 40 , 41 ]. Furthermore, squatting movements can be interpreted based on the principle of resistance training “specificity,” which enhances lower muscle strength and performance by reducing the time required to rise from a chair and increasing the number of 30-s chair stands [ 42 ]. Decreased lower muscle strength is directly associated with declines in basic activities of daily living, such as walking, standing up, and climbing stairs, and also increases the risk of falls. Maintaining lower muscle function from this timing is particularly crucial, as patients undergoing chemotherapy often experience pronounced muscle weakness, which negatively impacts mobility, daily functioning, and overall prognosis [ 43 , 44 ]. Limitations This study has some limitations. First, as a single-center prospective study, its generalizability is limited, as laboratory protocols and equipment for the assessment of physical function may vary across different centers, regions, or countries. Second, the patients included in this study were referred from public health checkups or local clinics to our specialist hospital for the examination and treatment of suspected lung cancer. As a result, their actual first visit occurred before they arrived at our hospital, making it difficult to strictly evaluate the study period from the true first visit. Third, one of the enrolled patients was ultimately diagnosed as showing no evidence of cancer. Since exercise guidance was provided from the initial visit until treatment initiation under the assumption of a possible cancer diagnosis, there is a possibility that this patient experienced unnecessary psychological distress related to the prospect of having cancer. To address this, we explained the possibility of a non-cancer diagnosis at the time of consent and emphasized the general benefits of physical activity for individuals regardless of their cancer status. Finally, as this was a feasibility study of an exercise program, its impact on overall survival, treatment efficacy, medical costs, and cachexia remains unknown. These aspects should be explored in future studies. Conclusions This study demonstrated that the combined slow squat and aerobic exercise program is a feasible and safe regimen from the first visit to treatment initiation. Furthermore, physical function and muscle strength were maintained or improved in patients with advanced lung cancer. The exercise program described here could, therefore, be adopted to prevent muscle weakness and loss of physical function from the first visit to the start of treatment, thereby increasing the effectiveness of cancer treatment and improving prognosis, we can propose a new approach to cancer treatment in the future. However, its effectiveness in improving cancer treatment outcomes should be confirmed in randomized controlled trials. Abbreviations ACSM, American College of Sports Medicine; CI, confidence interval; GPAQ, Global Physical Activity Questionnaire; HHD, hand-held dynamometer; HRQoL, health-related quality of life; MNA-SF, Mini Nutritional Assessment Short-Form; PD-L1, programmed cell death ligand 1; QoL, quality of life; SMI, skeletal muscle mass index Declarations Ethics approval and consent to participate: This study was approved by the Research Ethics Review Committee of Kansai Medical University Hospital, Osaka, Japan (approval number: 2024037), and was registered in the University hospital Medical Information Network (UMIN000055155). All patients provided informed consent after receiving a detailed explanation of the study. Consent for publication: Written informed consent was obtained from each participant. All procedures were performed in accordance with the ethical standards of the committees responsible for human experimentation (institutional and national) and the Declaration of Helsinki of 1964 and its later versions. Availability of data and materials: The data that support the findings of this study are available from the first author (U.K.) upon reasonable request. Competing interests: The authors declare that they have no competing interests Funding: This work was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research, Tokyo, Japan (C) [23K10572 to U.K.]. Authors' contributions: UK: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Data Curation, Writing - Original Draft, Visualization, Funding acquisition.TF: Investigation, Resources, Data Curation, Writing - Review & Editing, Supervision, Project administration. KF: Investigation. YN: Investigation. KK: Investigation. YO: Investigation. 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J Korean Med Sci. 2020;35:e242. 10.3346/jkms.2020.35.e242 . Courneya KS, Mackey JR, Bell GJ, Jones LW, Field CJ, Fairey AS. Randomized controlled trial of exercise training in postmenopausal breast cancer survivors: Cardiopulmonary and quality of life outcomes. J Clin Oncol. 2003;21:1660–8. 10.1200/JCO.2003.04.093 . Mustian KM, Alfano CM, Heckler C, Kleckner AS, Kleckner IR, Leach CR, et al. Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: A meta-analysis. JAMA Oncol. 2017;3:961–8. 10.1001/jamaoncol.2016.6914 . Westcott WL, Winett RA, Anderson ES, Wojcik JR, Loud RL, Cleggett E, et al. Effects of regular and slow speed resistance training on muscle strength. J Sports Med Phys Fit. 2001;41:154–8. Hermes MJ, Fry AC. Intentionally slow concentric velocity resistance exercise and strength adaptations: A meta-analysis. J Strength Cond Res. 2023;37:e470–84. 10.1519/JSC.0000000000004490 . Lee TD, Swanson LR, Hall AL. What is repeated in a repetition? Effects of practice conditions on motor skill acquisition. Phys Ther. 1991;71:150–6. 10.1093/ptj/71.2.150 . Marques VA, Ferreira-Junior JB, Lemos TV, Moraes RF, Junior JRS, Alves RR, et al. Effects of chemotherapy treatment on muscle strength, quality of life, fatigue, and anxiety in women with breast cancer. Int J Environ Res Public Health. 2020;17:7289. 10.3390/ijerph17197289 . Pin F, Couch ME, Bonetto A. Preservation of muscle mass as a strategy to reduce the toxic effects of cancer chemotherapy on body composition. Curr Opin Support Palliat Care. 2018;12:420–6. 10.1097/SPC.0000000000000382 . Tables Table 1. General and clinical characteristics of patients Characteristic Value Age, mean ± SD (years) 70 ± 9 Sex, no. [%] Male 14 [82.4] BMI, mean ± SD (kg/m 2 ) 21.4 ± 3.5 CRP, mean ± SD (mg/dL) 1.1 ± 1.8 Hemoglobin, mean ± SD (g/dL) 13.6 ± 1.2 Albumin, mean ± SD (g/dL) 4.1 ± 0.5 PS at T0, no. [%] 0 1 5 [9.4] 12 [70.6] Pathology, no. [%] Ad Sq Adsq NSCLC Sm 10 [58.8] 4 [23.5] 1 [5.9] 1 [5.9] 1 [5.9] Clinical stage, no. [%] I II IIIA IIIB IIIC IVA IVB 2 [11.8] 0 [0.0] 3 [17.6] 2 [11.8] 1 [5.9] 5 [29.4] 4 [23.5] Genetic mutation, no. [%] None EGFR KRAS Not evaluated 8 [47.1] 1 [5.9] 1 [5.9] 7 [41.2] PD-L1 tumor proportion score, no. [%] <1% 1–49% ≥50% Not evaluated 2 [11.8] 5 [29.4] 3 [17.6] 7 [41.2] Ad; adenocarcinoma; Adsq: adenosquamous cell carcinoma; BMI: body mass index; CRP: C-reactive protein; EGFR: epidermal growth factor receptor; KRAS: Kirsten rat sarcoma viral oncogene homolog; NSCLC: non-small cell lung cancer; PD-L1: programmed cell death ligand 1; PS: performance status; SD: standard deviation; Sm: Small cell carcinoma; Sq: squamous cell carcinoma; T0, first visit; T1, intervention period. Table 2. Patient comments on the intervention Exercise attendance rate Patient comments High (≥70.8%) N = 15 1. I have always liked to walk, so I tried to walk more. Squatting was quite difficult when I did it seriously. 2. I did the exercises properly. It was not that difficult. I usually walk a lot for work, but squatting made my legs feel stronger, so I preferred squats. I thought I had learned something useful, so I will continue doing them. 3. I suspected I might have cancer. I did not know why I was losing so much weight until I was diagnosed. After listening to the doctor, I decided to take exercise seriously and followed the routine. 4. Walking for a long time was difficult because my legs were weak. I tried to do squats in my own way, knowing they were beneficial for me. However, I found it hard to continue when it became too difficult. 5. I was depressed because I thought I might have cancer, but exercising helped me during that time. 8. I exercised every day. I have always been physically active at work, so exercise was not too difficult for me. 9. I followed the routine because I had made a commitment to my doctor. However, squats were challenging because my knees hurt. 10. My wife and I did squats three times a day. It did not take much time, was not too difficult, and was a good form of exercise. 11. I walked every day and did squats most days. I think I could have done more if I did not have a cough. 12. I got tired of squatting and switched to walking. Walking every day was manageable for me. 15. I often experience fever and shortness of breath, so I sometimes cannot walk. When I am unable to walk, I do squats instead. Doing ten squats in a row makes me slightly short of breath. 16. I exercised with the determination to stay strong for my treatment. I will continue exercising to maintain my physical strength. 17. Although exercising was difficult, I continued doing squats and walking. I do not like being told what to do, but I did it for my own benefit. 19. I did squats every day. When I performed them slowly and properly as instructed, they were quite tough. 20. I have always enjoyed physical exercise. When I felt anxious about my test results and future treatment, exercising helped me overcome my negative emotions. Squats alone were not enough for me, so I used dumbbells while squatting. Low (<70.8%) N = 2 6. I have never been in the habit of exercising. It is too hot outside, and there is a hill in front of my house, making it difficult for me to go out. Pain also made exercising challenging. 18. I have never been in the habit of exercising. I tried hard at first, but proper squats were too difficult for my knees, so I stopped halfway and switched to walking. I also struggled with keeping a diary. Table 3. Mean change in physical function, physical activity, nutritional status, and quality of life Variables T0 T1 Mean difference P -value Mean ± SD Mean ± SD (95% CI) Hand grip strength, kg 30.1 ± 8.6 30.9 ± 9.8 0.8 ［-0.2 to 1.9］ 0.093 Isometric knee extensor strength, kgf 29.9 ± 10.9 31.4 ± 12.1 1.5 ［-0.1 to 3.1］ 0.064 5TST, s 8.9 ± 2.9 7.5 ± 2.7 -1.4 ［-2.1 to -0.8］ <0.001 CS-30, times 18 ± 6 21 ± 6 3 ［2 to 4］ <0.001 6MWD, m 457 ± 118 468 ± 124 11 ［12 to 34］ 0.336 OLS, s 10.8 ± 5.4 11.4 ± 4.9 0.5 ［-0.5 to 1.5］ 0.276 SMI, kg/m 2 7.3 ± 0.9 7.4 ± 0.95 0.1 ［0.04 to 0.16］ 0.240 GPAQ, METs-min/week 6912.9 ± 7233.5 6864.7 ± 8746.6 48.2 ［-2186.7 to 2090.3］ 0.962 MNA-SF, points 9 ± 3 10 ± 3 1 ［0 to 2］ 0.135 EQ-5D-5L, points 0.81 ± 0.13 0.86 ± 0.12 0.05 ［-0.02 to 1.11］ 0.143 5TST: 5-times-sit-to-stand test; 6MWD: 6-minute walk distance; CI: confidence interval; CS-30: 30-s chair stand test; EQ-5D-5L: EuroQol 5-dimensions 5-level; GPAQ: Global Physical Activity Questionnaire; kgf, kilograms of force; MNA-SF: Mini Nutritional Assessment Short-Form; OLS: one-leg standing test; SMI: skeletal muscle index; T0, first visit; T1, intervention period. Additional Declarations No competing interests reported. Supplementary Files GA12March202501UK9.tif Cite Share Download PDF Status: Published Journal Publication published 29 Sep, 2025 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 20 Jun, 2025 Reviews received at journal 12 Jun, 2025 Reviewers agreed at journal 11 Jun, 2025 Reviews received at journal 22 May, 2025 Reviewers agreed at journal 21 May, 2025 Reviewers invited by journal 10 Apr, 2025 Editor assigned by journal 02 Apr, 2025 Submission checks completed at journal 02 Apr, 2025 First submitted to journal 02 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6341600","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":441103143,"identity":"0d75512b-78f5-4df9-b13d-106d42762dec","order_by":0,"name":"Utae Katsushima","email":"","orcid":"","institution":"Kansai Medical University","correspondingAuthor":false,"prefix":"","firstName":"Utae","middleName":"","lastName":"Katsushima","suffix":""},{"id":441103144,"identity":"db83d390-7a16-4b40-8a65-b332dc01a444","order_by":1,"name":"Takuya Fukushima","email":"","orcid":"","institution":"Kansai Medical 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Ochi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYFACHoYDHxuANDOYx0acloMzSdbCzNtAirP42c8ePGy7w8aen52B8cMPBr48gloke/ISDueeSUuc2czALNnDwFZMUIvBDR6Dw7lthxMMDjMwSAP9kkjQkWAtlm2H7e0PMzD/Jl4LY9thxg3MDGzE2SLZk2NwsLctLXEGUKNljwERfuFnP2P84WcbMMT6Dx++8aPiGOEQQwKMQCcZHEsgRQsY1JCuZRSMglEwCoY9AACg4DbjIdxDhQAAAABJRU5ErkJggg==","orcid":"","institution":"Hosei University","correspondingAuthor":true,"prefix":"","firstName":"Eisuke","middleName":"","lastName":"Ochi","suffix":""}],"badges":[],"createdAt":"2025-03-31 04:38:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6341600/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6341600/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-025-14728-2","type":"published","date":"2025-09-29T15:58:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80712544,"identity":"924966c8-8aae-4b46-8620-32e8a5d5e0d7","added_by":"auto","created_at":"2025-04-16 09:16:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":257315,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flow.\u003cstrong\u003e \u003c/strong\u003eA total of 24 patients were recruited; three were excluded, and 21 were enrolled. Of these, four patients dropped out, resulting in a final analysis of 17 patients.\u003c/p\u003e","description":"","filename":"Figure1UK9.png","url":"https://assets-eu.researchsquare.com/files/rs-6341600/v1/3b5d7341a829c08d1ceb0060.png"},{"id":92884100,"identity":"a6a85041-5e46-40fb-a8cf-75c8b9aa9612","added_by":"auto","created_at":"2025-10-06 16:12:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1211047,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6341600/v1/552fbbf8-cbfd-435f-bde1-3a9ab0fb10a5.pdf"},{"id":80712546,"identity":"a76a59b1-4e08-46f9-82ff-78396bf193d1","added_by":"auto","created_at":"2025-04-16 09:16:52","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":125632,"visible":true,"origin":"","legend":"","description":"","filename":"GA12March202501UK9.tif","url":"https://assets-eu.researchsquare.com/files/rs-6341600/v1/5b78f37b4cf45abab18b0060.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Combined effects of slow movement training with tonic force generation and aerobic exercise prior to cancer therapy in patients with lung cancer (START-lung): A pilot feasibility trial","fulltext":[{"header":"Background","content":"\u003cp\u003eLung cancer generally has a poor prognosis, with high mortality and morbidity rates [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, in recent years, prognosis has improved with the emergence of immune checkpoint inhibitors and molecular targeted therapies [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Specialized tests, such as the assessment of programmed cell death ligand 1 (PD-L1) expression and genetic mutation analysis, are required for a definitive diagnosis of lung cancer and to determine an appropriate treatment plan [\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePreviously, we reported that the median time from the first visit to the initiation of treatment was 37 days for early-stage lung cancer and 42.5 days for advanced lung cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. During this period, body and muscle weight, physical function, and nutritional status declined, which may contribute to the development of cachexia, particularly in patients with advanced lung cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Furthermore, physical function declines rapidly following a cancer diagnosis, and this decline tends to persist [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Notably, muscle weakness and reduced physical function have been associated with poor cancer prognosis [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, no studies have examined the safety and adherence rates of exercise interventions during this period in patients with advanced lung cancer.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to develop a structured exercise program for patients suspected of having advanced lung cancer to be implemented from the first visit to treatment initiation. We hypothesized that our exercise program could be safe, feasible, and prevent muscle weakness and physical function.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patients\u003c/h2\u003e \u003cp\u003eThis was a single-arm feasibility study involving a single-center prospective intervention conducted at Kansai Medical University.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003eMen and women aged\u0026thinsp;\u0026ge;\u0026thinsp;20 years (at the time of consent) with suspected advanced lung cancer and a scheduled first visit to the outpatient clinic for thorough examination and treatment were included in the study. All patients provided informed consent after receiving a detailed explanation of the study.\u003c/p\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003ePatients who had severe hepatic or renal dysfunction, were pregnant or lactating, had respiratory failure requiring oxygen therapy or severe pain interfering with physical function assessment, or were deemed unsuitable for participation by the principal investigator were excluded from the study.\u003c/p\u003e\n\u003ch3\u003eExercise protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eExercise protocol\u003c/div\u003e \u003cp\u003ePatients were advised to engage in home-based exercise for at least a total of 6 sessions per week, including a minimum of three resistance exercise sessions (slow squats) and three aerobic sessions (walking for at least 30 min per session) for 4 weeks. The first visit (T0) was defined as the day of the first visit\u0026thinsp;\u0026plusmn;\u0026thinsp;7 days, and the intervention period (T1) was 4\u0026thinsp;\u0026plusmn;\u0026thinsp;2 weeks from T0. Attendance was monitored through an exercise diary, with assessments conducted at both T0 and T1. The exercise diary was collected at T1 to gather patient feedback on adherence to the home-based exercise program.\u003c/p\u003e \u003cp\u003eAs recommended by the American College of Sports Medicine (ACSM) guidelines, the exercise program included both resistance and aerobic exercises, performed for at least 150 min per week [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. For resistance exercise, participants performed slow squats, a movement involving controlled force generation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. They were instructed to squat until their thighs were parallel to the floor over 4 s, then extend their knees over another 4 s. Patients were advised to complete three sets of 10\u0026ndash;15 repetitions for one session. If balance was a concern, they were permitted to hold onto a chair or wall for support. For aerobic exercise, patients were instructed to walk at moderate intensity (Borg scale: 12\u0026ndash;14). Each walking session lasted at least 30 min. At the first visit, a physician counseled patients on the role of exercise in cancer treatment, while a physiotherapist provided detailed instructions for the home-based exercise regimen.\u003c/p\u003e\n\u003ch3\u003eEndpoints\u003c/h3\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrimary endpoint\u003c/h2\u003e \u003cp\u003eThe primary endpoint was the attendance rates of exercise sessions. Based on the report by Adamsen et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], an attendance rate of 70.8% (17/24 sessions) or higher was considered feasible. This evaluation was based on exercise diaries, with attendance defined as the percentage of participant sessions out of six weekly sessions (24 total) over the 4-week period.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSecondary endpoints\u003c/h3\u003e\n\u003cp\u003eThe secondary endpoints included adverse events, physical activity (assessed using the Global Physical Activity Questionnaire [GPAQ]), health-related quality of life (QoL) (assessed using the EQ-5D), skeletal muscle mass, 6-min walk distance, grip strength, knee extensor strength, five-time chair stand test, 30-s stand test, one-leg stand time, and nutritional status (using the Mini Nutritional Assessment Short-Form [MNA-SF]). Additionally, lung cancer characteristics, baseline patient information, and blood laboratory data were collected from medical records.\u003c/p\u003e \u003cp\u003ePhysical activity\u003c/p\u003e \u003cp\u003eThe GPAQ was developed by the World Health Organization to assess physical activity and consists of 16 questions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It collects information on physical activity levels and sedentary behavior across three domains: work, mobility, and leisure-time activity. The GPAQ is a reliable tool for assessing physical activity levels in cancer survivors [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this study, patients were asked to complete the GPAQ at T0 and T1.\u003c/p\u003e \u003cp\u003eHealth-related QoL\u003c/p\u003e \u003cp\u003eThe EQ-5D is a standardized questionnaire for assessing health-related QoL (HRQoL). It consists of five components: mobility, personal care, daily activities, pain/discomfort, and anxiety/depression. Each component is rated on a 3- or 5-point scale to assess overall health status. In previous studies, the EQ-5D demonstrated adequate reliability and validity in assessing QoL in patients with cancer [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In this study, the EQ-5D was administered to patients at T0 and T1.\u003c/p\u003e \u003cp\u003eSkeletal Muscle Mass\u003c/p\u003e \u003cp\u003eA body composition analyzer (MC-780A-N, Tanita, Tokyo, Japan), utilizing the bioelectrical impedance analysis method, was used to evaluate body composition. From the data, we calculated the skeletal muscle mass index (SMI; kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003e6-Min Walk Distance\u003c/p\u003e \u003cp\u003eThe 6-min walk distance test is a simple and practical method for assessing functional exercise tolerance in patients [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In a straight, flat corridor, patients were instructed to walk for 6 min at the fastest, comfortable pace possible, continuing as long as they could. Resting was permitted if necessary. At the end of 6 min, the total walking distance (in meters) was recorded.\u003c/p\u003e \u003cp\u003eGrip strength\u003c/p\u003e \u003cp\u003eMuscle weakness was defined as grip strength\u0026thinsp;\u0026lt;\u0026thinsp;28 kg in men and \u0026lt;\u0026thinsp;18 kg in women, based on the diagnostic criteria for sarcopenia [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Grip strength was measured using a hand-held dynamometer (HHD) (GRIP-D; Takei Scientific Instruments Co., LTD, Niigata, Japan). One test was performed for each hand, and the result of the stronger hand was used for analysis.\u003c/p\u003e \u003cp\u003eKnee Extensor Strength\u003c/p\u003e \u003cp\u003eKnee extension strength serves as an indicator of quadriceps (front thigh) muscle strength, while knee flexion strength reflects biceps femoris (back thigh) muscle strength. In this study, an HHD was placed on each leg for two measurements, with the higher value recorded as the final strength measurement. For the assessment, patients were seated in a final sitting position, with the trunk held upright and arms crossed over the chest. Afterwards, the examiner positioned the HHD on the front surface of the patient\u0026rsquo;s distal lower leg, securing it with a fixation strap. The patient was then instructed to extend the knee with maximum force to measure isometric knee extension muscle strength [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFive-time chair stand test\u003c/p\u003e \u003cp\u003ePatients were instructed to sit in a chair with their arms crossed over their chest and their back against the chair. The time required to rise from a seated position to a full standing position and return to sitting five times was recorded. Muscle weakness was defined as a test duration of \u0026ge;\u0026thinsp;11.19 s[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e30-s chair stand test\u003c/p\u003e \u003cp\u003eThe 30-s chair stand test assesses lower limb muscle activity, balance ability, and walking speed. It is conducted by counting the number of times a participant can rise from a seated position in a chair within 30 s [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. For this test, participants were seated in a chair without armrests, with arms crossed over the chest, and were instructed to stand up and sit down repeatedly for 30 s. The total number of completed repetitions was recorded.\u003c/p\u003e \u003cp\u003eOne-leg standing test\u003c/p\u003e \u003cp\u003eWith both hands on the hips and eyes open, participants raised one leg 5 cm off the ground, and the duration of their balance was measured. After one or two practice trials, each leg was measured twice, with the longest recorded time used for analysis. Motor instability was defined as an inability to balance for more than 15 s on one leg [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNutritional status\u003c/p\u003e \u003cp\u003eNutritional status was assessed using the MNA-SF, an internationally standardized tool with established reliability and validity. The MNA-SF is a simple, efficient screening tool that requires no specialized knowledge or equipment and can be completed within minutes [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. It was administered to each patient on their first visit to the rehabilitation outpatient clinic.\u003c/p\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eThe expected rate of exercise implementation, the primary endpoint of this study, was set at 70.8% (attended 17/24 sessions) based on a study by Adamsen et al [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The threshold was set at 42\u0026thinsp;\u0026plusmn;\u0026thinsp;34%, based on findings from Mazzoni et al [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Statistical parameters were set as follows: alpha error\u0026thinsp;=\u0026thinsp;0.05, beta error\u0026thinsp;=\u0026thinsp;0.05. The required sample size was calculated as 17 participants. To account for a 20% dropout rate, the final target sample size was set at 21 participants. Each exercise session was counted as one implementation, regardless of the number of sets, resistance exercises, or the duration of aerobic exercise. For secondary endpoints, data collected at T0 and T1 were presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Paired \u003cem\u003et\u003c/em\u003e-tests were used to compare measurements at T0 and T1, with mean differences and 95% confidence interval (CI) calculated. The significance level was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003e This study was approved by the Research Ethics Review Committee of Kansai Medical University Hospital, Osaka, Japan (approval number: 2024037), and was registered in the University hospital Medical Information Network (UMIN000055155). Written informed consent was obtained from each participant. All procedures were performed in accordance with the ethical standards of the committees responsible for human experimentation (institutional and national) and the Declaration of Helsinki of 1964 and its later versions.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient enrollment and baseline characteristics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 24 patients were recruited between August 1 and October 28, 2024. As illustrated in the flowchart (Figure 1), one patient declined participation due to general fatigue, another was uninterested in exercise, and a third withdrew due to fatigue and pain. Ultimately, 21 patients were enrolled. However, two patients developed obstructive pneumonia between the first visit and the start of treatment; one patient died due to disease progression, and another was excluded from the analysis after a benign tumor was diagnosed following further examination. Consequently, the final cohort for analysis included 17 patients. The baseline characteristics of these 17 patients are presented in Table 1. The mean age was 70 years, with 14 men (82.4%) and three women (17.6%). At the first visit, five patients (29.4%) had a performance status (PS) of 0, while 12 patients (70.6%) had a PS of 1. The stage of disease at confirmed diagnosis varied, with two cases (11.8%) classified as stage I, three cases (17.6%) as stage IIIA, two cases (11.8%) as stage IIIB, one case (5.9%) as stage IIIC, five cases (29.4%) as stage IVA, and four cases (23.5%) as stage IVB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOverall exercise attendance rate\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall exercise attendance rate was 159.7 \u0026plusmn; 54.4%. Among the 17 patients, 15 patients maintained a high attendance rate (attended at least 70.8%), while two patients demonstrated low attendance. Patient feedback regarding exercise participation at T1 is summarized in Table 2. Among the 15 patients with a high exercise attendance rate, several had pre-existing exercise habits, while others credited family support as a motivating factor. Some found that exercising provided emotional stability, whereas others believed it would impact their cancer treatment by contributing to build muscle strength and dispelling anxiety. In the two cases with a low exercise attendance rate, physical symptoms, prior exercise preferences, and environmental factors contributed to non-adherence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSafety\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 17 patients, there were no apparent adverse events associated with the exercise program.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eChanges in physical activity, QoL, Skeletal Muscle Mass, physical function, and nutritional status from the first visit to the start of treatment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs summarized in Table 3, the patients demonstrated significant improvements in both the five-times-sit-to-stand test (mean difference: -1.4 s, 95% CI: -2.1 to -0.8 s, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) and 30-s chair stand tests (mean difference: 3 times, 95% CI: 2 to 4 times,\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) after exercise intervention. However, no significant changes were observed in muscle strength (grip strength mean difference: 0.8 kg, 95% CI: -0.2 to 1.9 kg, \u003cem\u003ep\u003c/em\u003e=0.093; isometric knee extensor strength mean difference: 1.5 kgf; 95% CI: -0.1 to 3.1 kgf; \u003cem\u003ep\u003c/em\u003e=0.064), physical function (6MWD mean difference: 11 m, 95% CI 12 to 34 m, \u003cem\u003ep\u003c/em\u003e=0.336; OLS mean difference: 0.5 s, 95% CI: -0.5 to 1.5 s, \u003cem\u003ep\u003c/em\u003e=0.276), muscle mass (SMI mean difference: 0.1 kg/m\u003csup\u003e2\u003c/sup\u003e, 95% CI: 0.04 to 0.16 kg/m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u003c/em\u003e=0.240), nutritional status (MNA-SF mean difference: 1 point, 95% CI: 0 to 2 points, \u003cem\u003ep\u003c/em\u003e=0.135), physical activity (GPAQ mean difference: 48.2 min/week, 95％ CI: -2186.7 to 2090.3 min/week,\u003cem\u003ep\u003c/em\u003e＝0.962), or QoL (EQ5d-5L mean difference: 0.05 points, 95% CI: -0.02 to 1.11, \u003cem\u003ep\u003c/em\u003e=0.143).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is the first prospective trial to evaluate the feasibility of exercise during the period between a patient\u0026rsquo;s initial visit to an outpatient clinic and the start of lung cancer treatment. This investigation is particularly novel, as no previous clinical trials have examined exercise interventions from the time of the first visit for suspected lung cancer to the start of treatment, a period even earlier than conventional pre-treatment exercise interventions. The results of this study support our hypothesis, demonstrating that our exercise program was exceptionally feasible and safe.\u003c/p\u003e \u003cp\u003eExercise in cancer survivors has been shown to reduce mortality and recurrence risk, alleviate cancer-related fatigue, improve QoL, reduce depression and anxiety, enhance sleep quality, and improve cardiorespiratory function [\u003cspan additionalcitationids=\"CR30 CR31 CR32\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The American Cancer Society and the American College of Sports Medicine recommend a combination of 150 min of moderate-intensity aerobic exercise per week and at least two sessions of resistance training [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, in the absence of studies defining a feasible and optimal exercise regimen for patients with cancer during the period between their initial outpatient visit for suspected advanced lung cancer and definitive diagnosis, we based our guidance on the above recommendations. Our results demonstrated a high attendance rate of 159.7\u0026thinsp;\u0026plusmn;\u0026thinsp;54.4%. Previous studies have reported that exercise programs for patients with advanced lung cancer often face challenges such as high dropout rates and low adherence [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Furthermore, while supervised exercise interventions have been shown to be feasible for patients with advanced cancer [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], the feasibility of implementing home-based exercise programs has remained unclear. This study confirmed the high feasibility of aerobic exercise and slow squats, which are simple and easily integrated into daily routines [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Furthermore, patient feedback indicated that these exercises could be performed year-round, regardless of weather conditions or living environment, and without requiring specialized equipment or designated space. These factors likely contributed to the high attendance rate observed in our study. However, various physical symptoms, such as pain and shortness of breath, along with individual exercise preferences, lifestyle factors, and living environment, may act as barriers to adherence. In addition, the waiting period between a patient\u0026rsquo;s first visit\u0026mdash;when they receive the distressing news that they may have cancer\u0026mdash;and the start of treatment following diagnostic tests is often marked by heightened anxiety regarding their prognosis and treatment course. In the present study, educating patients about the significance of exercise in cancer treatment at the time of the first visit may have facilitated behavioral changes, leading to a high exercise attendance rate. In addition, the benefits of exercise on fatigue, QoL, and depression in patients with cancer have been previously reported [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Patient feedback suggests that engaging in exercise from the initial visit to the start of treatment not only improves physical function but may also help alleviate mental distress, including anxiety and depression.\u003c/p\u003e \u003cp\u003eA previous study reported significant weight loss, deterioration in nutritional status, and reduced grip strength between the first visit and the start of treatment [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, notably, the results of this study demonstrated that exercise therapy during this period prevented an obvious decline in physical function, nutritional status, or QoL. Moreover, improvements were observed in the five-time sit-to-stand and 30-s chair stand (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), both indicators of lower limb muscle strength. It showed that the slow squat causes increases in muscle mass and strength by sustaining tonic muscle contractions and generating continuous force production [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Furthermore, squatting movements can be interpreted based on the principle of resistance training \u0026ldquo;specificity,\u0026rdquo; which enhances lower muscle strength and performance by reducing the time required to rise from a chair and increasing the number of 30-s chair stands [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Decreased lower muscle strength is directly associated with declines in basic activities of daily living, such as walking, standing up, and climbing stairs, and also increases the risk of falls. Maintaining lower muscle function from this timing is particularly crucial, as patients undergoing chemotherapy often experience pronounced muscle weakness, which negatively impacts mobility, daily functioning, and overall prognosis [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study has some limitations. First, as a single-center prospective study, its generalizability is limited, as laboratory protocols and equipment for the assessment of physical function may vary across different centers, regions, or countries. Second, the patients included in this study were referred from public health checkups or local clinics to our specialist hospital for the examination and treatment of suspected lung cancer. As a result, their actual first visit occurred before they arrived at our hospital, making it difficult to strictly evaluate the study period from the true first visit. Third, one of the enrolled patients was ultimately diagnosed as showing no evidence of cancer. Since exercise guidance was provided from the initial visit until treatment initiation under the assumption of a possible cancer diagnosis, there is a possibility that this patient experienced unnecessary psychological distress related to the prospect of having cancer. To address this, we explained the possibility of a non-cancer diagnosis at the time of consent and emphasized the general benefits of physical activity for individuals regardless of their cancer status. Finally, as this was a feasibility study of an exercise program, its impact on overall survival, treatment efficacy, medical costs, and cachexia remains unknown. These aspects should be explored in future studies.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrated that the combined slow squat and aerobic exercise program is a feasible and safe regimen from the first visit to treatment initiation. Furthermore, physical function and muscle strength were maintained or improved in patients with advanced lung cancer. The exercise program described here could, therefore, be adopted to prevent muscle weakness and loss of physical function from the first visit to the start of treatment, thereby increasing the effectiveness of cancer treatment and improving prognosis, we can propose a new approach to cancer treatment in the future. However, its effectiveness in improving cancer treatment outcomes should be confirmed in randomized controlled trials.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACSM, American College of Sports Medicine; CI, confidence interval; GPAQ, Global Physical Activity Questionnaire; HHD, hand-held dynamometer; HRQoL, health-related quality of life; MNA-SF, Mini Nutritional Assessment Short-Form; PD-L1, programmed cell death ligand 1; QoL, quality of life; SMI, skeletal muscle mass index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e This study was approved by the Research Ethics Review Committee of Kansai Medical University Hospital, Osaka, Japan (approval number: 2024037), and was registered in the University hospital Medical Information Network (UMIN000055155). All patients provided informed consent after receiving a detailed explanation of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Written informed consent was obtained from each participant. All procedures were performed in accordance with the ethical standards of the committees responsible for human experimentation (institutional and national) and the Declaration of Helsinki of 1964 and its later versions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the first author (U.K.) upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This work was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research, Tokyo, Japan (C) [23K10572 to U.K.].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e UK: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Data Curation, Writing - Original Draft, Visualization, Funding acquisition.TF: Investigation, Resources, Data Curation, Writing - Review \u0026amp; Editing, Supervision, Project administration. KF: Investigation. YN: Investigation. KK: Investigation. YO: Investigation. KY: Investigation. TI: Investigation. YT: Investigation. YY: Investigation. HY: Investigation. TK: Writing - Review \u0026amp; Editing, Supervision. EO: Conceptualization, Methodology, Writing - Review \u0026amp; Editing, Supervision.\u0026nbsp;All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Effects of chemotherapy treatment on muscle strength, quality of life, fatigue, and anxiety in women with breast cancer. Int J Environ Res Public Health. 2020;17:7289. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijerph17197289\u003c/span\u003e\u003cspan address=\"10.3390/ijerph17197289\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePin F, Couch ME, Bonetto A. Preservation of muscle mass as a strategy to reduce the toxic effects of cancer chemotherapy on body composition. Curr Opin Support Palliat Care. 2018;12:420\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/SPC.0000000000000382\u003c/span\u003e\u003cspan address=\"10.1097/SPC.0000000000000382\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eGeneral and clinical characteristics of patients\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"583\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eAge, mean \u0026plusmn; SD (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e70 \u0026plusmn; 9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eSex, no. [%]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 [82.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eBMI, mean \u0026plusmn; SD (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e21.4 \u0026plusmn; 3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eCRP, mean \u0026plusmn; SD (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e1.1 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eHemoglobin, mean \u0026plusmn; SD (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e13.6 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eAlbumin, mean \u0026plusmn; SD (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e4.1 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003ePS at T0, no. [%]\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 [9.4]\u003c/p\u003e\n \u003cp\u003e12 [70.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003ePathology, no. [%]\u003c/p\u003e\n \u003cp\u003eAd\u003c/p\u003e\n \u003cp\u003eSq\u003c/p\u003e\n \u003cp\u003eAdsq\u003c/p\u003e\n \u003cp\u003eNSCLC\u003c/p\u003e\n \u003cp\u003eSm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 [58.8]\u003c/p\u003e\n \u003cp\u003e4 [23.5]\u003c/p\u003e\n \u003cp\u003e1 [5.9]\u003c/p\u003e\n \u003cp\u003e1 [5.9]\u003c/p\u003e\n \u003cp\u003e1 [5.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eClinical stage, no. [%]\u003c/p\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003cp\u003eIIIA\u003c/p\u003e\n \u003cp\u003eIIIB\u003c/p\u003e\n \u003cp\u003eIIIC\u003c/p\u003e\n \u003cp\u003eIVA\u003c/p\u003e\n \u003cp\u003eIVB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 [11.8]\u003c/p\u003e\n \u003cp\u003e0 [0.0]\u003c/p\u003e\n \u003cp\u003e3 [17.6]\u003c/p\u003e\n \u003cp\u003e2 [11.8]\u003c/p\u003e\n \u003cp\u003e1 [5.9]\u003c/p\u003e\n \u003cp\u003e5 [29.4]\u003c/p\u003e\n \u003cp\u003e4 [23.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003eGenetic mutation, no. [%]\u003c/p\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eEGFR\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eKRAS\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNot evaluated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 [47.1]\u003c/p\u003e\n \u003cp\u003e1 [5.9]\u003c/p\u003e\n \u003cp\u003e1 [5.9]\u003c/p\u003e\n \u003cp\u003e7 [41.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 397px;\"\u003e\n \u003cp\u003ePD-L1 tumor proportion score, no. [%]\u003c/p\u003e\n \u003cp\u003e\u0026lt;1%\u003c/p\u003e\n \u003cp\u003e1\u0026ndash;49%\u003c/p\u003e\n \u003cp\u003e\u0026ge;50%\u003c/p\u003e\n \u003cp\u003eNot evaluated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 [11.8]\u003c/p\u003e\n \u003cp\u003e5 [29.4]\u003c/p\u003e\n \u003cp\u003e3 [17.6]\u003c/p\u003e\n \u003cp\u003e7 [41.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAd; adenocarcinoma; Adsq: adenosquamous cell carcinoma; BMI: body mass index; CRP: C-reactive protein; EGFR: epidermal growth factor receptor; KRAS: Kirsten rat sarcoma viral oncogene homolog; NSCLC: non-small cell lung cancer; PD-L1: programmed cell death ligand 1; PS: performance status; SD: standard deviation; Sm: Small cell carcinoma; Sq: squamous cell carcinoma; T0, first visit; T1, intervention period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003ePatient comments on the intervention\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExercise attendance rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 393px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Patient comments\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eHigh (\u0026ge;70.8%) \u003cem\u003eN\u003c/em\u003e = 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 393px;\"\u003e\n \u003cp\u003e\u0026nbsp;1. I have always liked to walk, so I tried to walk more. Squatting was quite difficult when I did it seriously.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2. I did the exercises properly. It was not that difficult. I usually walk a lot for work, but squatting made my legs feel stronger, so I preferred squats. I thought I had learned something useful, so I will continue doing them.\u003c/p\u003e\n \u003cp\u003e3. I suspected I might have cancer. I did not know why I was losing so much weight until I was diagnosed. After listening to the doctor, I decided to take exercise seriously and followed the routine.\u003c/p\u003e\n \u003cp\u003e4. Walking for a long time was difficult because my legs were weak. I tried to do squats in my own way, knowing they were beneficial for me. However, I found it hard to continue when it became too difficult.\u003c/p\u003e\n \u003cp\u003e5. I was depressed because I thought I might have cancer, but exercising helped me during that time.\u003c/p\u003e\n \u003cp\u003e8. I exercised every day. I have always been physically active at work, so exercise was not too difficult for me.\u003c/p\u003e\n \u003cp\u003e9. I followed the routine because I had made a commitment to my doctor. However, squats were challenging because my knees hurt.\u003c/p\u003e\n \u003cp\u003e10. My wife and I did squats three times a day. It did not take much time, was not too difficult, and was a good form of exercise.\u003c/p\u003e\n \u003cp\u003e11. I walked every day and did squats most days. I think I could have done more if I did not have a cough.\u003c/p\u003e\n \u003cp\u003e12. I got tired of squatting and switched to walking. Walking every day was manageable for me.\u003c/p\u003e\n \u003cp\u003e15. I often experience fever and shortness of breath, so I sometimes cannot walk. When I am unable to walk, I do squats instead. Doing ten squats in a row makes me slightly short of breath.\u003c/p\u003e\n \u003cp\u003e16. I exercised with the determination to stay strong for my treatment. I will continue exercising to maintain my physical strength.\u003c/p\u003e\n \u003cp\u003e17. Although exercising was difficult, I continued doing squats and walking. I do not like being told what to do, but I did it for my own benefit.\u003c/p\u003e\n \u003cp\u003e19. I did squats every day. When I performed them slowly and properly as instructed, they were quite tough.\u003c/p\u003e\n \u003cp\u003e20. I have always enjoyed physical exercise. When I felt anxious about my test results and future treatment, exercising helped me overcome my negative emotions. Squats alone were not enough for me, so I used dumbbells while squatting.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eLow (\u0026lt;70.8%) \u003cem\u003eN\u003c/em\u003e = 2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 393px;\"\u003e\n \u003cp\u003e6. I have never been in the habit of exercising. It is too hot outside, and there is a hill in front of my house, making it difficult for me to go out. Pain also made exercising challenging.\u003c/p\u003e\n \u003cp\u003e18. I have never been in the habit of exercising. I tried hard at first, but proper squats were too difficult for my knees, so I stopped halfway and switched to walking. I also struggled with keeping a diary.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eMean change in physical function, physical activity, nutritional status, and quality of life\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"593\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean difference\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eHand grip strength, kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e30.1 \u0026plusmn; 8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e30.9 \u0026plusmn; 9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.8\u0026nbsp;［-0.2 to 1.9］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eIsometric knee extensor strength, kgf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e29.9 \u0026plusmn; 10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e31.4 \u0026plusmn; 12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.5\u0026nbsp;［-0.1 to 3.1］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e5TST, s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e8.9 \u0026plusmn; 2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e7.5 \u0026plusmn; 2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e-1.4\u0026nbsp;［-2.1 to -0.8］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eCS-30, times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e18 \u0026plusmn; 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e21 \u0026plusmn; 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3\u0026nbsp;［2 to 4］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e6MWD, m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e457 \u0026plusmn; 118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e468 \u0026plusmn; 124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e11\u0026nbsp;［12 to 34］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.336\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eOLS, s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e10.8 \u0026plusmn; 5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e11.4 \u0026plusmn; 4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.5\u0026nbsp;［-0.5 to 1.5］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eSMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e7.3 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e7.4 \u0026plusmn; 0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.1\u0026nbsp;［0.04 to 0.16］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eGPAQ, METs-min/week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e6912.9 \u0026plusmn; 7233.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e6864.7 \u0026plusmn; 8746.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e48.2\u0026nbsp;［-2186.7 to 2090.3］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.962\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eMNA-SF, points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e9 \u0026plusmn; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e10 \u0026plusmn; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1\u0026nbsp;［0 to 2］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eEQ-5D-5L, points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.81 \u0026plusmn; 0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0.86 \u0026plusmn; 0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.05\u0026nbsp;［-0.02 to 1.11］\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e5TST: 5-times-sit-to-stand test; 6MWD: 6-minute walk distance; CI: confidence interval; CS-30: 30-s chair stand test; EQ-5D-5L: EuroQol 5-dimensions 5-level; GPAQ: Global Physical Activity Questionnaire; kgf, kilograms of force; MNA-SF: Mini Nutritional Assessment Short-Form; OLS: one-leg standing test; SMI: skeletal muscle index; T0, first visit; T1, intervention period.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"advanced lung cancer, aerobic exercise, muscle strength, physical function, feasibility, slow training","lastPublishedDoi":"10.21203/rs.3.rs-6341600/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6341600/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eExercise is known to improve physical function, quality of life, and treatment outcomes in patients with cancer. However, the feasibility and impact of implementing an exercise program from the first visit for suspected advanced lung cancer to treatment initiation remain unclear. This study aimed to evaluate the feasibility of a structured exercise program during this period.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective, single-center study included patients with suspected advanced lung cancer who were instructed to perform a pre-treatment 4-week exercise program consisting of slow movement training with tonic force generation and aerobic exercise. Attendance rates and adverse events were assessed, and changes in physical function, muscle strength, and quality of life were evaluated. Patient feedback on the exercise program was collected.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 17 patients were analyzed, with a mean age of 70 years. The overall exercise attendance rate was 159.7\u0026thinsp;\u0026plusmn;\u0026thinsp;54.4%. A high attendance rate (\u0026ge;\u0026thinsp;70.8%) was achieved by 15 patients without any adverse events. Significant improvements from baseline to after-exercise intervention were observed in the five-time sit-to-stand test and 30-second chair stand test. No significant changes in physical function, muscle strength, or quality of life were observed. Patient feedback indicated that exercise was beneficial in alleviating anxiety and maintaining physical condition during the waiting period before treatment.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eA structured exercise program initiated from the first visit to treatment initiation was feasible and safe in patients with advanced lung cancer. Further studies, including randomized controlled trials, are warranted to assess its impact on clinical outcomes and long-term patient wellbeing.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eUMIN000055155. Date of registration: August 5, 2024.\u003c/p\u003e","manuscriptTitle":"Combined effects of slow movement training with tonic force generation and aerobic exercise prior to cancer therapy in patients with lung cancer (START-lung): A pilot feasibility trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 09:16:47","doi":"10.21203/rs.3.rs-6341600/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-20T04:36:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-12T06:37:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"173502347733264318477280275853928641734","date":"2025-06-11T08:41:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-22T22:20:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"269068589491889513291792183800721593169","date":"2025-05-21T07:02:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-10T08:27:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-02T15:19:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-02T06:20:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-04-02T06:19:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5b4444c0-75c2-4013-a2ac-f4495abb2d0d","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:08:13+00:00","versionOfRecord":{"articleIdentity":"rs-6341600","link":"https://doi.org/10.1186/s12885-025-14728-2","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2025-09-29 15:58:10","publishedOnDateReadable":"September 29th, 2025"},"versionCreatedAt":"2025-04-16 09:16:47","video":"","vorDoi":"10.1186/s12885-025-14728-2","vorDoiUrl":"https://doi.org/10.1186/s12885-025-14728-2","workflowStages":[]},"version":"v1","identity":"rs-6341600","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6341600","identity":"rs-6341600","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}